A world-renowned UI scientist confronts the complex mystery of muscular dystrophy.
On most Saturdays, the schedule goes like this. Kevin Campbell rises and treks to the Java House for a cappuccino or two. He mows the grass around his eastside Iowa City home and takes his nine-year-old white Labrador, Max, for their daily walk.
Then, if he's lucky, out of the ordinary comes the extraordinary.
As he pushes his Lawn-Boy and brings Max to a heel, Campbell is immersed in thought. Despite outward appearances to the contrary, he's working. He's always working, his brain whizzing and whirring toward answers to a most devastating illness-one that robs thousands of children of their ability to walk and run and, finally, to draw a breath. He works seven days a week and around the clock, often waking in the middle of the night to jot down whatever thoughts jolt him from sleep.
Internationally recognized for his groundbreaking muscular dystrophy research, Campbell says, "It's the chaos in my mind that leads to novel ideas."
The resulting "eureka!" moments are rare, but they occur. And it's the persistent cerebral noise that ranks Campbell among the University of Iowa's most brilliant scientists. The UI's Roy J. Carver Chair of Biomedical Research, he is also professor and head of molecular physiology and biophysics, professor of internal medicine and neurology, a member of the National Academy of Sciences, and one of only 354 Howard Hughes Medical Institute investigators in the United States.
Earlier this year, Campbell received the 2009 March of Dimes Prize in Developmental Biology for his pioneering discovery of genes and proteins that cause several forms of muscular dystrophy, a genetic disease that leads to progressive muscle weakness and wasting. Such breakthroughs have provided crucial insights into how muscular dystrophies develop, improving diagnosis and potential treatments.
But it's not the carrot of recognition that sparks Campbell's quest. It is for boys like 11-year-old Alex Carlson that the scientist persists.
Alex is one of more than 250,000 Americans who suffer from the nine forms of muscular dystrophy (MD), a figure that climbs to one million when taking into account the multiple other neuromuscular disorders supported by the Muscular Dystrophy Association. The various types of MD differ in severity, the age of onset, muscles affected, and the rate at which degeneration progresses. However, the disease is by and large an affliction associated with childhood. Although muscular dystrophies do strike girls, Duchenne-the most common and severe form-only impacts young boys, affecting one out of every 3,000 newborns for whom survival into adulthood is rare.
Most boys with Duchenne inherit an X-linked gene from their mothers (often carriers who exhibit no symptoms). First, the disease targets the hips, pelvic area, thighs, and shoulders-eventually sapping the strength of all muscles, including those that power the heart and lungs. Symptoms tend to show up anywhere from age two to six. For Alex, now a sixth-grader from Monticello, the first signs appeared in kindergarten. He couldn't run like other children or climb stairs.
Blood and genetics tests revealed Duchenne, although Alex proved a bit of an anomaly because he didn't inherit a faulty gene from his mom, Kim. Instead, an insertion (basically an extra letter) in his DNA sequence decided his fate.
Following Alex's diagnosis, and after four months of incapacitating grief and making deals with God, Kim Carlson says her family embraced a new motto. "You can either have a disease or the disease can have you," she says. "We chose the former. We have this, but we're going to live our lives the best way we know how."
Alex embraces his family motto with zeal. An easygoing kid who likes to tell jokes, he flat-out tells you the truth: "I can't do that because my muscles don't work like yours." He plays Wii, reads science-fiction books, and wrestles with his little brother, Jeff, who shows no evidence of Duchenne.
Up until he was about nine years old, the progression of Alex's MD proved fairly slow; he only had to begin using a wheelchair last year. Even now he looks on the bright side-he may not play football, but he's the honorary team manager, and he recently "ran" the 40-yard dash in his electric wheelchair.
Alex is the 2009 Iowa MDA Goodwill Ambassador, one of the faces that inspire firefighters everywhere to participate in MDA's Fill the Boot campaign each year. He's also one of the kids who inspire Jerry Lewis to host the annual Labor Day Telethon, among history's most successful medical research fund-raisers.
While Campbell has never met the Carlsons personally, he remains their steadfast champion. Campbell, whose own father suffered from another kind of muscle-weakening disease, started out as a basic scientist, interested in questions that didn't have any direct relevance to muscular dystrophy. He was curious about the structure and function of calcium channels in skeletal muscle (which controls movement of the skeleton), and it became clear to him that these channels were critical to muscle contraction. He wondered if disruptions in their function possibly played a role in muscular dystrophy. What began as a little side project to investigate this correlation became the crux of his research-and the challenge of his days.
The key discovery of Campbell's celebrated career came in 1989, eight years after he arrived at the UI. Campbell found that the protein of the Duchenne muscular dystrophy gene-dystrophin-was tightly associated with the muscle membrane. As he researched the function of this protein, Campbell made his biggest breakthrough to date. He identified the dystrophin-glycoprotein complex, a network of proteins that crucially maintains the structural integrity of muscle cell membranes and protects individual muscle cells from damage as they stretch and contract. Without dystrophin, muscle cells ultimately degenerate. Campbell discovered that alterations and mutations in this protein network cause not only Duchenne, but also several other forms of MD.
As head of the UI Department of Molecular Physiology and Biophysics, Campbell continues to investigate the nature of the dystrophin-glycoprotein complex. He works from and directs the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, a sprawling facility in the Carver Biomedical Research Building on the UI campus. Established in 2005 with a $7.3 million grant from the National Institutes of Health (NIH), the center honors former Minnesota Democrat Paul Wellstone, a vocal supporter of Duchenne research.
A year before his death in 2002, Wellstone introduced legislation mandating that the NIH establish centers of excellence for basic and clinical research into Duchenne and other forms of muscular dystrophy (in 2005, the UI was only the fourth institution to receive such funding). Like its partners across the country, the UI Wellstone Center has three main goals: explore the basic biological mechanisms that relate to possible treatments for muscular dystrophy; facilitate translational research on MD; and provide advanced diagnostic services to patients and clinical trial participants. The center also provides tours to families.
The lab employs undergraduate students and postdoctoral fellows alike who use biochemical tools and modern genetic approaches to decode the mysteries of MD. Here, Campbell and his colleagues employ a wide range of scientific tools-from the basic Petri dish to the world's most advanced data-storing computers-to outwit an elusive, complicated enemy. Here, alongside his team, the scientist tests the thoughts and theories that could lead to true progress.
In one area of the lab, a research assistant opens the door of a liquid nitrogen freezer and retrieves muscle and other tissue samples provided by both mice and humans. At another station, a lab worker peers through a microscope to examine thin slices of muscle and membrane, looking for signs of health or disease, anything that's missing or abnormal. Over there, tiny pieces of tissue shake and stir in a DNA solution to reveal genetic markers. In yet another quiet corner, a biochemist isolates and studies individual cells, trying to locate their proteins. The process is tedious and repetitive and a little bit miraculous.
"This is my vocation and avocation mixed together," says Campbell, when asked what has kept him motivated throughout two decades of MD research, when discoveries and puzzle pieces come together only after years and years of painstaking work. "It's thrilling when someone sends me a result that reveals something unknown or an idea we'd never thought about. I'm absolutely addicted to figuring out these problems."
One of Campbell's priority projects is an investigation into whether improving muscle membrane maintenance and repair can provide a basis for new treatments for Duchenne. He previously pinpointed important roles in muscle function for two proteins known as "LARGE" and "dysferlin"-and he's been able to restore normal muscle function in mice that model this form of MD. Now, Campbell's team studies whether increasing levels of either or both of these proteins produces a therapeutic effect. If so, the discovery could one day lead to protein-modifying drugs that benefit patients.
Thanks to research like this in Campbell's lab and other Wellstone centers, several clinical trials are now under way across the country to develop drug therapies that could potentially slow disease progression or reverse muscle damage. Nonetheless, Campbell confesses that he and scientists like him don't really think in terms of cures. While the push is always for a cure-and that is certainly the highest ideal, the dream-Campbell points out that science has found few actual cures for diseases. Vaccinations help ward off diseases such as polio and measles, but major killers such as cancer, AIDS, and diabetes continue to cut short human life. Instead, Campbell applies his energy toward slowing down a disease process, causing its retreat and improving a person's quality of life.
As a mother, Kim Carlson admits she wishes for Campbell to find a cure. But she knows the realities, and so she'll gladly accept any measure of relief for her son. "I just really hope they can find a stop-gap measure," Carlson says. "Anything that would stop his disease where it is right now."
Until then, the Carlson family treks to Iowa City every six months so doctors at UI Hospitals and Clinics can evaluate Alex's muscle strength and administer an echocardiogram to monitor his heart. For now, the Carlsons express gratitude for the daily routine and celebrate the special occasions, like a recent vacation to explore U.S. Civil War sites. Alex looks forward to other bright spots, like his adventures during MD week at Camp Courageous. Just down the road from his home, Camp Courageous welcomes 100 campers from across the U.S. each year, who gather in Iowa to share their own brave fights against muscular dystrophy. Mostly, though, they come to just enjoy the experiences that every child loves to have under a hot summer sun.
They take a dip in the pool and a canoe trip on the water; they delight in the tug of a fish on a line and songs by the fire at night. Abandoning canes and walkers and wheelchairs, they take turns on a cable that sends them soaring between the trees.
Meanwhile, back in Iowa City, Kevin Campbell stays the course. He tinkers in the yard, pours Max a bowl of kibble, and consults with experts near and far about his latest inspiration. Every second, he presses forward in his tireless quest for an answer that will give children like Alex more than a brief taste of freedom-more than a brief chance at life.